The structure-function relationship between peptide aldehyde derivatives on initiation of neurite outgrowth in PC12h cells.
We have previously shown that, among many protease inhibitors examined, only a leupeptin analogue, Ac-Leu-Leu-Nle-al (ALLNal), induces neurite outgrowth in PC12h cells. Since this neurite outgrowth is different from that induced by nerve growth factor (NGF) in terms of morphology and persistence, the existence of a specific protease which regulates neurite formation in PC12h cells was expected. A set of 10 ALLNal analogue peptide protease inhibitors was synthesized and examined for their potency in inducing neurite outgrowth in PC12h cells. Substitution of the N-terminal acetyl residue in ALLNal by benzyloxycarbonyl (Z) increased the activity by about 4 times. For Z-Leu-Leu-X-al, neurite outgrowth was induced in the following order: Leu greater than Phe greater than Nva greater than Val = Ile = Nle greater than Ala greater than Gly at the X residue. The potency of Z-Leu-Leu-Leu-al (ZLLLal) was 50-fold stronger than that of ALLNal. ZLLLal provides a strong tool for characterizing this new type of protease.
Saito
Y
Y
Department of Biochemistry, Tokyo Metropolitan Institute of Gerontology, Japan.
Tsubuki
S
S
Ito
H
H
Kawashima
S
S
D000310:Adrenal Gland Neoplasms; D000447:Aldehydes / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D002460:Cell Line; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D010673:Pheochromocytoma; D051381:Rats; D013329:Structure-Activity Relationship
D000447:Aldehydes; D009414:Nerve Growth Factors; D009842:Oligopeptides